Differential diagnosis of consciousness disorders

Brojna stanja u medicini, od hipoglikemije do traumatskih intrakranijalnih krvarenja, kao vodeći simptom imaju promijenjenu svijest. Ta razdoblja promijenjene svijesti mogu trajati od nekoliko sekunda (primjerice, u sinkopi) do nekoliko dana i tjedana, pa sve do toga da pojedini pacijenti čitav život provedu s protrahiranim poremećajima svijesti kao što su minimalno svjesno stanje (minimally conscious state, MCS) ili perzistentno vegetativno stanje (PVS). Kako su napreci u medicinskoj znanosti i tehnologiji omogućili dulje preživljenje pacijenata u stanjima poremećene svijesti, svakim danom raste na važnosti problem njihovog međusobnost razlikovanja i ranog prepoznavanja njihovih uzroka. Osnova za uspostavljanje ispravne dijagnoze poremećaja svijesti je, možda više nego li igdje drugdje u kliničkoj neurologiji, dobro poznavanje neuroanatomije i dobra vještina primjene tog znanja na ispitivanje neurološkog statusa. Ascendentni retikularni aktivacijski sustav (ARAS) moždanog debla, koji sadrži glavne strukture za regulaciju budnosti i spavanja, smješten je blizu jezgara čija se funkcija može klinički ispitati čak i u pacijenata bez svijesti, što omogućuje lokalizaciju potencijalne strukturalne lezije i procjenu štete. Radiološke, laboratorijske i elektrofiziološke pretrage služe daljnjem prepoznavanju različitih uzroka poremećaja svijesti. Ovaj rad ima za cilj dati kratak pregled tih uzroka, patofiziologije oštećenja koja stvaraju i specifičnosti u njihovoj manifestaciji na osnovi kojih se mogu razlikovati. Utvrđivanje potpunog prestanka moždane aktivnosti, poznatog kao moždana smrt, je također svakim danom sve relevantnije pitanje, a od posebne je važnosti u transplantacijskoj medicini.A wide spectrum of disorders, ranging from intracranial hemorrhage to hypoglycemia, present with impaired consciousness as a leading symptom. The duration of these periods of impaired consciousness varies from less than a minute (for example, in syncope) to days and weeks at a time, with certain patients confined to a lifetime of disordered consciousness in states such as minimally conscious state (MCS) and persistent vegetative state (PVS). As improvements in medical science and technology increase the survival of patients in states of impaired consciousness, the problem of properly differentiating between these states and recognizing their causes early on steadily grows in importance. The basis for establishing a correct diagnosis of these disorders is, perhaps even more so than in other areas of clinical neurology, a strong grasp of neuroanatomy and its skillful application in the neurological examination. The ascending reticular activating system (ARAS) of the brainstem, the main pathway regulating wakefulness and sleep, lies in close proximity to certain nuclei whose function can be clinically tested even in unconscious patients, allowing for localization of a potential focal lesion and assessment of damage. Neuroimaging, laboratory testing and electrophysiological studies can further identify different levels and causes of consciousness disorders. This paper aims to review these potential causes, the pathophysiology of the damage they cause and the specificities in their manifestation that can be used to differentiate between them. Determining the complete absence of brain activity, also known as “brain death”, is an increasingly important issue, especially relevant in transplantation medicine

Differential diagnosis of consciousness disorders

Brojna stanja u medicini, od hipoglikemije do traumatskih intrakranijalnih krvarenja, kao vodeći simptom imaju promijenjenu svijest. Ta razdoblja promijenjene svijesti mogu trajati od nekoliko sekunda (primjerice, u sinkopi) do nekoliko dana i tjedana, pa sve do toga da pojedini pacijenti čitav život provedu s protrahiranim poremećajima svijesti kao što su minimalno svjesno stanje (minimally conscious state, MCS) ili perzistentno vegetativno stanje (PVS). Kako su napreci u medicinskoj znanosti i tehnologiji omogućili dulje preživljenje pacijenata u stanjima poremećene svijesti, svakim danom raste na važnosti problem njihovog međusobnost razlikovanja i ranog prepoznavanja njihovih uzroka. Osnova za uspostavljanje ispravne dijagnoze poremećaja svijesti je, možda više nego li igdje drugdje u kliničkoj neurologiji, dobro poznavanje neuroanatomije i dobra vještina primjene tog znanja na ispitivanje neurološkog statusa. Ascendentni retikularni aktivacijski sustav (ARAS) moždanog debla, koji sadrži glavne strukture za regulaciju budnosti i spavanja, smješten je blizu jezgara čija se funkcija može klinički ispitati čak i u pacijenata bez svijesti, što omogućuje lokalizaciju potencijalne strukturalne lezije i procjenu štete. Radiološke, laboratorijske i elektrofiziološke pretrage služe daljnjem prepoznavanju različitih uzroka poremećaja svijesti. Ovaj rad ima za cilj dati kratak pregled tih uzroka, patofiziologije oštećenja koja stvaraju i specifičnosti u njihovoj manifestaciji na osnovi kojih se mogu razlikovati. Utvrđivanje potpunog prestanka moždane aktivnosti, poznatog kao moždana smrt, je također svakim danom sve relevantnije pitanje, a od posebne je važnosti u transplantacijskoj medicini.A wide spectrum of disorders, ranging from intracranial hemorrhage to hypoglycemia, present with impaired consciousness as a leading symptom. The duration of these periods of impaired consciousness varies from less than a minute (for example, in syncope) to days and weeks at a time, with certain patients confined to a lifetime of disordered consciousness in states such as minimally conscious state (MCS) and persistent vegetative state (PVS). As improvements in medical science and technology increase the survival of patients in states of impaired consciousness, the problem of properly differentiating between these states and recognizing their causes early on steadily grows in importance. The basis for establishing a correct diagnosis of these disorders is, perhaps even more so than in other areas of clinical neurology, a strong grasp of neuroanatomy and its skillful application in the neurological examination. The ascending reticular activating system (ARAS) of the brainstem, the main pathway regulating wakefulness and sleep, lies in close proximity to certain nuclei whose function can be clinically tested even in unconscious patients, allowing for localization of a potential focal lesion and assessment of damage. Neuroimaging, laboratory testing and electrophysiological studies can further identify different levels and causes of consciousness disorders. This paper aims to review these potential causes, the pathophysiology of the damage they cause and the specificities in their manifestation that can be used to differentiate between them. Determining the complete absence of brain activity, also known as “brain death”, is an increasingly important issue, especially relevant in transplantation medicine

SEXUAL DYSFUNCTION IN PATIENTS WITH EPILEPSY

Background: Patients with epilepsy commonly report sexual dysfunction (SD) and reproductive difficulties. This study aimed to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and SD, and its association with the quality of life and depressive symptoms. Subjects and methods: This was a prospective study carried out in a tertiary healthcare centre. SD was evaluated using the internationally acclaimed questionnaire Arizona Sexual Experiences Scale (ASEX) that was successfully translated into Croatian and validated for this purpose. Depressive symptoms and quality of life were evaluated using the Hamilton Rating Scale for Depression (HAM-D17) and Quality of life in epilepsy-31 inventory (QOLIE-31). Results: Of 108 patients (68 (63 %) women, 40 (37 %) men, mean age 39.54±15.91 (range18-80) years) with epilepsy, 16 (14.8%) had focal, 38 (35.2%) generalized and 44 (40.7%) both types of epilepsy. Mean overall total score on the ASEX questionnaire was 11.94±5.61 (mean total score women 12.85±6.00, mean total score men 10.4±4.55), with 48 reporting that they had sexual activity in the past week. Nine (8.33%) patients (7 (6.48%) women, 2 (1.85%) men, mean age 47.66±19.33 (range 25-80) years) had a score 19 and above, 38 (35.18%) patients (27 (25%) women, 9 (8.33%) men, mean age 46.82±17.78 (range 19-80) years) individual score 5 and above on any one item, and 33 (30.55%) patients (26 (24.07%) women, 7 (6.48%) men, mean age 48.87±17.8 (range 19-80) years) had an individual score 4 and above on any three items. Significant correlations were found between SD and older age (p=0.001) and between more pronounced symptoms regarding SD on ASEX and female gender (p=0.000). There were no significant correlations between the type of epilepsy and SD, nor between the AEDs (old generation vs. modern) and SD. Significant correlations were found between the SD and more pronounced depressive symptoms (p=0.003) and between the SD and a lower quality of life (p=0.001). Conclusions: Results of our study suggest SD is experienced by around one-third of patients in our group, which is similar to the previous percentage of SD reported in the community sample. Women were found to experience more pronounced symptoms of SD on ASEX. Symptoms of SD were found to be significantly correlated with older age, female gender, lower quality of life and depressive symptoms, while no significant correlations were found with the type of epilepsy and the AEDs

DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH EPILEPSY - SINGLE CENTRE EXPERIENCE

Background: Patients with epilepsy commonly report depressive symptoms. The main aim of this study was to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and depression. We also wanted to evaluate possible association between depressive symptofigms in patients with epilepsy with the quality of life (QoL). Material and methods: This was a prospective cross-sectional study carried out at the tertiary teaching hospital (University Hospital Centre Zagreb, Croatia) with Ethics committee approval. Questionnaires evaluating depressive symptoms and QoL were administered to consecutive patients treated in the Referral Centre of the Ministry of Health of the Republic of Croatia for Epilepsy. Depressive symptoms were evaluated using Hamilton Rating Scale for Depression (HAM-D17). Quality of life was assessed using Quality of life in epilepsy-31 inventory (QOLIE-31) Results: 108 patients (63% women, 37% men; mean age 39.54±15.91 years, range 18-80 years) with epilepsy were included. 14.8% of patients had focal, 35.2% generalised and 40.7% both types of epilepsy. Majority of patients (65.74%) were on two and more AEDs and quarter was on monotherapy (25%); 42% were on newer, 19% on older and 39% on both AEDs. Mean total score on HAM-D17 was 9.94±8.18 (men - mean total score 10.16±8.85, women - mean total score 9.81±7.84). There were no significant differences on HAM- newer AEDs, or both types AEDs) and results on HAM-D17, nor between the type of epilepsy and results on HAM-D17. We found strong negative correlation between the higher QoL and HAM-D17 (p=0.000). Conclusions: Results of this study evaluating depressive symptoms in patients with epilepsy demonstrate that our patients mainly experience mild depressive symptoms, with no significant differences on HAM-D17 regarding gender and age. Patients with epilepsy with less pronounced depressive symptoms were found to have higher QoL. We did not find statistically significant differences regarding the type of epilepsy and results on HAM-D17, nor between the AEDs (older vs. newer AEDs, or both types AEDs) and results on HAM-D17

Kvaliteta života bolesnika s epilepsijom - naša iskustva

A prospective study was carried out at the Zagreb University Hospital Centre to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and quality of life (QoL) in patients with epilepsy (PE), and its association with depressive symptoms and sexual dysfunction (SD). QoL was assessed by use of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31), SD by the Arizona Sexual Experiences Scale (ASEX), and depressive symptoms by the Hamilton Rating Scale for Depression (HAM-D17). The study included 108 PE (women 63% and men 37% men), mean age 39.54±15.91 years. Focal type epilepsy was diagnosed in 14.8%, generalized type in 35.2%, and both types were present in 40.7% of study patients. Drug-resistant epilepsy (DRE) was present in 44/108 and vagus nerve stimulation (VNS) was implanted in 27/44 patients. The mean response on QOLIE-31 was 62.88±17.21 with no significant differences according to gender, type of epilepsy, and age. A statistically significantly lower QoL was found in the ‘Overall QoL’ domain (35-55 vs. <35 age group). Patients taking both types of AEDs had a significantly lower QoL compared to those on newer types of AEDs. Higher QoL was associated with less pronounced depressive symptoms (p=0.000). Significant correlations were found between lower QoL and SD (p=0.001). In 27 patients with DRE having undergone VNS, a favorable effect of VNS implantation on the QoL and mood was observed as compared with 18 patients without VNS (p=0.041).Provedeno je prospektivno istraživanje u KBC-u Zagreb s ciljem procjene povezanosti epilepsije, antiepileptičkih lijekova (antiepileptic drug, AED) i kvalitete života (quality of life, QoL) u bolesnika s epilepsijom, kao i učestalosti depresije i seksualne disfunkcije (SD). QOLIE-31 (Quality of Life in Epilepsy-31 Inventory) je primijenjen za procjenu QoL-a, ASEX (Arizona Sexual Experiences Scale) za SD i HAM-D17 (Hamilton Rating Scale) za depresiju. Uključeno je 108 bolesnika s epilepsijom (63% žena, 37% muškaraca; srednja dob 39,54±15,91 godina). Žarišnu epilepsiju imalo je 14,8% i generaliziranu 35,2% bolesnika, dok je obje vrste epilepsije imalo 40,7% bolesnika. Farmakorezistentnu epilepsiju (drug-resistant epilepsy, DRE) imalo je 44/108 bolesnika, a kod njih 27/44 ugrađen je stimulator vagusnog živca (vagus nerve stimulation, VNS). Srednji odgovor na QOLIE-31 bio je 62,88±7,21 bez značajnih razlika u odnosu na spol, vrstu epilepsije i dob. Statistički značajno niži QoL nađen je u domeni ‘Sveukupni QoL’ (dobna skupina 35-55 godina u odnosu na dobnu skupinu <35). Bolesnici koji su uzimali obje vrste AED imali su značajno niži QoL u usporedbi s onima na novijim AED. Viši QoL bio je povezan s manje izraženim simptomima depresije (p=0,000). Pronađene su značajne korelacije između nižeg QoL-a i SD (p=0,001). U bolesnika s DRE utvrđen je pozitivan utjecaj ugradnje VNS-a na QoL i raspoloženje (27 bolesnika s VNS-om u usporedbi s 18 bolesnika bez VNS-a, p=0,041)

Differential diagnosis of consciousness disorders

Brojna stanja u medicini, od hipoglikemije do traumatskih intrakranijalnih krvarenja, kao vodeći simptom imaju promijenjenu svijest. Ta razdoblja promijenjene svijesti mogu trajati od nekoliko sekunda (primjerice, u sinkopi) do nekoliko dana i tjedana, pa sve do toga da pojedini pacijenti čitav život provedu s protrahiranim poremećajima svijesti kao što su minimalno svjesno stanje (minimally conscious state, MCS) ili perzistentno vegetativno stanje (PVS). Kako su napreci u medicinskoj znanosti i tehnologiji omogućili dulje preživljenje pacijenata u stanjima poremećene svijesti, svakim danom raste na važnosti problem njihovog međusobnost razlikovanja i ranog prepoznavanja njihovih uzroka. Osnova za uspostavljanje ispravne dijagnoze poremećaja svijesti je, možda više nego li igdje drugdje u kliničkoj neurologiji, dobro poznavanje neuroanatomije i dobra vještina primjene tog znanja na ispitivanje neurološkog statusa. Ascendentni retikularni aktivacijski sustav (ARAS) moždanog debla, koji sadrži glavne strukture za regulaciju budnosti i spavanja, smješten je blizu jezgara čija se funkcija može klinički ispitati čak i u pacijenata bez svijesti, što omogućuje lokalizaciju potencijalne strukturalne lezije i procjenu štete. Radiološke, laboratorijske i elektrofiziološke pretrage služe daljnjem prepoznavanju različitih uzroka poremećaja svijesti. Ovaj rad ima za cilj dati kratak pregled tih uzroka, patofiziologije oštećenja koja stvaraju i specifičnosti u njihovoj manifestaciji na osnovi kojih se mogu razlikovati. Utvrđivanje potpunog prestanka moždane aktivnosti, poznatog kao moždana smrt, je također svakim danom sve relevantnije pitanje, a od posebne je važnosti u transplantacijskoj medicini.A wide spectrum of disorders, ranging from intracranial hemorrhage to hypoglycemia, present with impaired consciousness as a leading symptom. The duration of these periods of impaired consciousness varies from less than a minute (for example, in syncope) to days and weeks at a time, with certain patients confined to a lifetime of disordered consciousness in states such as minimally conscious state (MCS) and persistent vegetative state (PVS). As improvements in medical science and technology increase the survival of patients in states of impaired consciousness, the problem of properly differentiating between these states and recognizing their causes early on steadily grows in importance. The basis for establishing a correct diagnosis of these disorders is, perhaps even more so than in other areas of clinical neurology, a strong grasp of neuroanatomy and its skillful application in the neurological examination. The ascending reticular activating system (ARAS) of the brainstem, the main pathway regulating wakefulness and sleep, lies in close proximity to certain nuclei whose function can be clinically tested even in unconscious patients, allowing for localization of a potential focal lesion and assessment of damage. Neuroimaging, laboratory testing and electrophysiological studies can further identify different levels and causes of consciousness disorders. This paper aims to review these potential causes, the pathophysiology of the damage they cause and the specificities in their manifestation that can be used to differentiate between them. Determining the complete absence of brain activity, also known as “brain death”, is an increasingly important issue, especially relevant in transplantation medicine

Circadian Rhythm and Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis

Outpatient treatment of pneumonia in a setting with and without an infectious disease doctor

Aim: To compare the outpatient treatment of community acquired pneumonia (CAP) by infectious disease doctors (IDDs) and doctors of other specialties (nIDDs). Methods: We retrospectively identified 600 outpatients with CAP: 300 treated by IDDs and 300 by nIDDs in two tertiary hospitals during 2019. The two groups were compared in terms of adherence to guidelines, antibiotic group prescription, frequency of combined treatment, and treatment duration. Results: IDDs prescribed significantly more first-line treatment (P<0.001) and alternative treatment (P=0.008). NIDDs prescribed more reasonable (P<0.001) and unnecessary (P=0.002) second-line treatment, and inadequate treatment (P=0.004). IDDs significantly more frequently prescribed amoxicillin (P<0.001) for typical and doxycycline (P=0.045) for atypical CAP, while nIDDs significantly more frequently prescribed amoxicillin-clavulanate (P<0.001) for typical and fluoroquinolones for both typical (P<0.001) and atypical (P<0.001) CAP. No significant differences were found in the frequency of combined treatment, which exceeded 50% in both groups, or in treatment duration. Conclusions: Outpatient treatment of CAP in the absence of IDDs meant more broad-spectrum antibiotic prescription and more disregard for national guidelines. Our results highlight the need for antibiotic stewardship, especially in settings with no IDDs